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Article: A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer

TitleA conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer
Authors
Issue Date2015
Citation
Nature Genetics, 2015, v. 47, n. 1, p. 47-56 How to Cite?
Abstract© 2015 Nature America, Inc. All rights reserved. Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse model and correlates with lymph node metastasis in human patients with pancreatic cancer. The propensity of piggyBac for open chromatin also enabled genome-wide screening for cancer-relevant noncoding DNA, which pinpointed a Cdkn2a cis-regulatory region. Histologically, we observed different tumor subentities and discovered associated genetic events, including Fign insertions in hepatoid pancreatic cancer. Our studies demonstrate the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis, such as downstream targets of commonly mutated human cancer genes. These piggyBac resources are universally applicable in any tissue context and provide unique experimental access to the genetic complexity of cancer.
Persistent Identifierhttp://hdl.handle.net/10722/249123
ISSN
2017 Impact Factor: 27.125
2015 SCImago Journal Rankings: 23.762
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRad, Roland-
dc.contributor.authorRad, Lena-
dc.contributor.authorWang, Wei-
dc.contributor.authorStrong, Alexander-
dc.contributor.authorPonstingl, Hannes-
dc.contributor.authorBronner, Iraad F.-
dc.contributor.authorMayho, Matthew-
dc.contributor.authorSteiger, Katja-
dc.contributor.authorWeber, Julia-
dc.contributor.authorHieber, Maren-
dc.contributor.authorVeltkamp, Christian-
dc.contributor.authorEser, Stefan-
dc.contributor.authorGeumann, Ulf-
dc.contributor.authorÖllinger, Rupert-
dc.contributor.authorZukowska, Magdalena-
dc.contributor.authorBarenboim, Maxim-
dc.contributor.authorMaresch, Roman-
dc.contributor.authorCadiñanos, Juan-
dc.contributor.authorFriedrich, Mathias-
dc.contributor.authorVarela, Ignacio-
dc.contributor.authorConstantino-Casas, Fernando-
dc.contributor.authorSarver, Aaron-
dc.contributor.authorTen Hoeve, Jelle-
dc.contributor.authorProsser, Haydn-
dc.contributor.authorSeidler, Barbara-
dc.contributor.authorBauer, Judith-
dc.contributor.authorHeikenwälder, Mathias-
dc.contributor.authorMetzakopian, Emmanouil-
dc.contributor.authorKrug, Anne-
dc.contributor.authorEhmer, Ursula-
dc.contributor.authorSchneider, Gönter-
dc.contributor.authorKnösel, Thomas-
dc.contributor.authorRömmele, Petra-
dc.contributor.authorAust, Daniela-
dc.contributor.authorGrötzmann, Robert-
dc.contributor.authorPilarsky, Christian-
dc.contributor.authorNing, Zemin-
dc.contributor.authorWessels, Lodewyk-
dc.contributor.authorM Schmid, Roland-
dc.contributor.authorA Quail, Michael-
dc.contributor.authorVassiliou, George-
dc.contributor.authorEsposito, Irene-
dc.contributor.authorLiu, Pentao-
dc.contributor.authorSaur, Dieter-
dc.contributor.authorBradley, Allan-
dc.date.accessioned2017-10-27T05:59:10Z-
dc.date.available2017-10-27T05:59:10Z-
dc.date.issued2015-
dc.identifier.citationNature Genetics, 2015, v. 47, n. 1, p. 47-56-
dc.identifier.issn1061-4036-
dc.identifier.urihttp://hdl.handle.net/10722/249123-
dc.description.abstract© 2015 Nature America, Inc. All rights reserved. Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse model and correlates with lymph node metastasis in human patients with pancreatic cancer. The propensity of piggyBac for open chromatin also enabled genome-wide screening for cancer-relevant noncoding DNA, which pinpointed a Cdkn2a cis-regulatory region. Histologically, we observed different tumor subentities and discovered associated genetic events, including Fign insertions in hepatoid pancreatic cancer. Our studies demonstrate the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis, such as downstream targets of commonly mutated human cancer genes. These piggyBac resources are universally applicable in any tissue context and provide unique experimental access to the genetic complexity of cancer.-
dc.languageeng-
dc.relation.ispartofNature Genetics-
dc.titleA conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ng.3164-
dc.identifier.pmid25485836-
dc.identifier.scopuseid_2-s2.0-84964312485-
dc.identifier.volume47-
dc.identifier.issue1-
dc.identifier.spage47-
dc.identifier.epage56-
dc.identifier.eissn1546-1718-
dc.identifier.isiWOS:000346990400011-
dc.identifier.f1000725267790-

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